Carbon nanotubes (1, 2) and semi-conducting nanowires (3) hold particular advantage in sensor applications because their 1-D electronic structure renders electron transport more sensitive to scattering from adsorbates than intrinsic mechanisms (2, 4, 5). Hence, these materials have spawned a host of new conductimetric sensors and array elements (3, 5, 6). Recent advances in the understanding of their optical properties (10, 11, 23) offer the possibility of using such materials as solution phase sensors (7, 8) that respond to analyte adsorption by modulation of optical properties, e.g., modulation of fluorescence emission. Such sensors could be implanted, for example, into human tissue (9) to provide real-time information about biochemical concentrations non-invasively.
Carbon nanotubes fluoresce in the near infrared (10, 11) and certain types (e.g., single walled carbon nanotubes (SWNTs) fluoresce from 900 to 1600 nm) do so in a region where human tissue and fluids, e.g., whole blood, (12) are particularly transparent to emission due to greater penetration and reduced auto-fluorescent background. Furthermore, SWNTs have particular advantage as sensing elements because all atoms of the nanotube are surface atoms making the nanotube especially sensitive to surface adsorption events. However, the ability to design sensors from carbon nanotubes is limited by fundamental limitations in our current ability to simultaneously control the electronic, chemical and colloidal properties of nanoparticle systems. Addition information on the properties of carbon nanotubes is found in the art (52-57.)
For use in selective optical sensor applications for the detection of analytes, carbon nanotubes must retain their ability to luminesce, they must be capable of interacting selectively with the analyte to be detected, and the selective interaction with the analyte must affect carbon nanotube luminescence. Nanotubes in electrical contact with each other do not luminesce because the excited state is depopulated non-irradiatively through inter-tube energy transfer (10). However, van der Waals forces provide large thermodynamic driving forces for aggregation of carbon nanotubes. For nanotubes to luminesce, they must be colloidally stabilized (to minimize or avoid aggregation). Individual fluorescent carbon nanotubes have been suspended after high energy ultrasonication using charged surfactants (10, 11, 13), non-ionic polymers (10, 22), and certain DNA sequences (14, 15). However, these interfaces interfere with the adsorption of charged reagents (17, 15) either via columbic interactions, or steric repulsion.
PCT published application WO03/050332 relates to the preparation of stable carbon nanotube dispersions in liquids. PCT published application WO02/095099 relates to noncovalent sidewall functionalization of carbon nanotubes.
PCT published application WO02/16257 relates to polymer wrapped single wall carbon nanotubes.
PCT published application WO03/102020 reports a method for obtaining peptides which bind to carbon nanotubes and other carbon nanostructures. Libraries containing peptides, typically a random mixture of peptides, are selected for their binding affinity for carbon nanotubes. Details of the method are given. A number of peptides of specific peptide sequence were identified as having binding affinity for carbon nanostructures, including carbon nanotubes. The sequences of a number of such peptides, particularly a set of peptides having 12 amino acids, were provided in the published application.
In addition, dispersed nanotubes exhibit more prominent resonant Raman scatter which is more sensitive to the environment of the nanotube (17), which may be useful in sensing applications.
Functionality must be associated with the carbon nanotube to provide for selective interaction with analytes. The inherent selectivities of biological molecules might, for example, be employed to provide for selective interaction of carbon nanotubes with analytes. However, to remain useful for sensing applications, nanotube functionalization must not disrupt nanotube optical properties (5). While it is possible to chemically attach functional groups to singly dispersed nanotubes (16), covalent functionalization of carbon nanotubes necessarily disrupts the 1-D electronic structure and desired optical properties (5, 16, 23, 24). Functionalization chemistries necessarily result in a rupturing of the conjugated π-cloud along the nanotube, disrupt its optical transitions and destroy fluorescence. Non-covalent modification using electroactive species, although difficult to control (17), provide a means of both preserving the carbon nanotube electronic structure (since no bonds are broken) and creating sites for selective binding.
The current state of carbon nanotube chemistry is therefore paradoxical: one must chemically modify the nanotube to impart desired functionality and selectivity toward analytes, but in doing so the 1-D electronic structure is disrupted destroying the ability to detect analyte interaction. Additionally, an encapsulating phase (e.g., surfactant) must be used to isolate the nanotube for colloidal stability and retention of fluorescence, and yet the stabilized nanotube must be accessible to facilitating molecular recognition.
The present invention provides solutions to the limitations discussed above and provides optical sensors and methods for the selective detection of analytes employing carbon nanotubes, particularly SWNTs.